| 1. |
- Andre, Kadri, et al.
(författare)
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SERT and NET polymorphisms, temperament and antidepressant response
- 2015
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 69:7, s. 531-538
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Tidskriftsartikel (refereegranskat)abstract
- Background: The genetic variations in norepinephrine transporter (NET) and serotonin transporter (SERT) genes have been associated with personality traits, several psychiatric disorders and the efficacy of antidepressant treatment. Aims: We investigated the separate effects and possible interactions between NET T-182C (rs2242446) and SERT 5-HTTLPR (rs4795541) polymorphisms on selective serotonin reuptake inhibitors (SSRI) treatment response and temperamental traits assessed by the Temperament and Character Inventory (TCI) in a clinical sample of subjects with major depressive disorder (MDD). Methods: Our sample of 97 patients with major depression completed the 107-item TCI temperament questionnaire (version IX) at the initial assessment of the study and after 6 weeks of follow-up. All subjects received selective SSRI medications. Temperament dimension scores at baseline (1) and endpoint (2) during antidepressant treatment were analyzed between NET and SERT genotypes. Results: SS-genotype of 5-HTTLPR was associated with higher baseline Persistence scores than SL- or LL-genotype. A corresponding but weaker association was found at endpoint. No differences were found between 5-HTTLPR genotypes and other temperament dimensions and 5-HTTLPR genotypes had no effect on treatment response. Conclusions: Our results suggest that the SS-genotype of 5-HTTLPR is associated with Persistence scores in patients with MDD. Higher Persistence could be viewed as a negative trait when recovering from stress and its association with short and "weaker" S-allele may be related to less efficient serotonin neurotransmission, possibly resulting in less effective coping strategies on a behavioral level.
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| 2. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 3. |
- Kautto, Mervi, et al.
(författare)
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Serotonin transporter (5-HTTLPR) and norepinephrine transporter (NET) gene polymorphisms : Susceptibility and treatment response of electroconvulsive therapy in treatment resistant depression
- 2015
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 590, s. 116-120
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Tidskriftsartikel (refereegranskat)abstract
- Serotonin transporter (5-HTTLPR) and norepinephrine transporter (NET182C) polymorphisms are associated with susceptibility and treatment response in major depressive disorder (MDD). Thus, we examined association between these polymorphisms and susceptibility to treatment resistant depression, and treatment response in severe MDD patients treated with electroconvulsive therapy (ECT).In total, 119 Finnish patients with treatment resistant depression and 395 healthy volunteer blood donors were genotyped. Depression severity was assessed using the Montgomery-Asberg Depression Scale (MADRS), with MADRS score change during ECT the treatment response indicator.Underrepresentation of the 5-HTTLPR 1/1 genotype in the NET TT subgroup was observed in patients compared with controls. There were no genotype or allele frequency differences between patients and control groups separately. Patients with combined 5-HTTLPR 1/1 and NET TT genotypes also had poorer treatment responses than other patients. No differences in ECT response were observed when the polymorphisms were examined separately.Our results suggest that a NET 182C and 5-HTTLPR polymorphism interaction is associated with susceptibility to treatment resistant depression and ECT treatment response in antidepressant resistant depression patients. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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